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Herombopag Added to Cyclosporine in Non Severe Aplastic Anemia

Primary Purpose

Non Severe Aplastic Anemia, Untreated

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Herombopag
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Severe Aplastic Anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Willing and able to comply with the requirements for this study and written informed consent. Male or female age ≥ 18 years Diagnosis of untreated non severe aplastic anemia. Platelet counts < 50 x 10^9/L at least 2 times consecutively (time interval ≥ 1 week) Exclusion Criteria: Receive immunosuppressive therapy more than 4 weeks before enrollment Treatment with TPO-RA within 1 week before enrollment Inherited bone marrow failure syndromes Bone marrow fibrosis grade ≥ 2 The presence of hemolytic PNH clone The presence of clonal karyotypic abnormalities (del(20q), +8 and -Y are not included in this category) Previously treated with TPO-RA ≥ 4 weeks Previously received immunosuppressive therapy ≥ 12 weeks Ferritin > 1000 ng/ml (The increased level of Ferritin led by infection is not included in this category) Have an allergy to eltrombopag or any other part of this medicine. History of radiotherapy and chemotherapy for malignant solid tumors Cytopenia caused by other non-hematologic diseases, including liver cirrhosis, active rheumatic connective tissue disease, and persistence of infectious diseases, etc Abnormal liver function: ALT or AST > 3 ULN, or TBil > 1.5 ULN after treatment. Abnormal kidney function: Creatinine clearance < 30 ml/min, or serum creatinine (sCr) >1.5 ULN Patients with diabetic nephropathy, neuropathy, or eye disease Patients with poorly controlled hypertension or cardiac arrhythmia Patients with congestive heart failure and the NYHA grade ≥ 3 historically or currently, and LVEF < 45% within 4 weeks before enrollment History of arteriovenous thrombosis within 1 year before enrollment Participation in another clinical trial within 4 months before the start of this trial Pregnant or breast-feeding patients Patients considered to be ineligible for the study by the investigator for reasons other than the above

Sites / Locations

  • Tangshan Central Hospital
  • Zhoukou Central Hospital
  • The Second Affilated Hospital of Shandong First Medical University
  • Regenerative Medicine CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CsA + Herombopag

Arm Description

Herombopag combined with cyclosporine

Outcomes

Primary Outcome Measures

Overall response rate
Percentage of patients with hematological response. Hematological response is evaluated by hemoglobin, platelet and neutrophil count in the routine blood test.

Secondary Outcome Measures

Robust response rate
Percentage of patients with robust response, including complete response, near complete response, very good partial response(VGPR) and Meaningful partial response(mPR). These are evaluated by hemoglobin, platelet and neutrophil count in the routine blood test.
Proportion of patients with abnormal karyotype changes
The abnormal karyotype was examined by karyotype test
Time duration for patients achieving hematological response
Duration time was calculated from response to relapse.
Change of the health-related quality of life
Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) is used to assess the health-related quality of life of patients. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100. Lower scores = more disability, higher scores = less disability
Incidence of the adverse event
Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event.
Severity of the adverse event
Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the severity.

Full Information

First Posted
November 23, 2022
Last Updated
December 14, 2022
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Jiangsu Hengrui Pharmaceuticals Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05660785
Brief Title
Herombopag Added to Cyclosporine in Non Severe Aplastic Anemia
Official Title
The Efficacy and Safety of Herombopag Combined With Cyclosporine for Patients With Non Severe Aplastic Anemia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2022 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
May 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Jiangsu Hengrui Pharmaceuticals Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective, multicenter, single-arm, phase 2 trial. The aim of this study is to evaluate the efficacy and safety of herombopag combined with cyclosporine for patients with non severe aplastic anemia (NSAA).
Detailed Description
This study aims to improve the 24 weeks response rate. The sample size is calculated based on Simon's two-stage design. The first stage of the study enrolled a cohort of 15 patients. If after 24 weeks at least 9 patients achieved a response, then enrollment was expanded to a total of 43 patients. The null hypothesis was unaccepted if more than 26 of 43 patients achieved the response. Accounting for a 20% dropout rate, the estimated final sample size was 54 patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Severe Aplastic Anemia, Untreated

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CsA + Herombopag
Arm Type
Experimental
Arm Description
Herombopag combined with cyclosporine
Intervention Type
Drug
Intervention Name(s)
Herombopag
Other Intervention Name(s)
Cyclosporine A
Intervention Description
Hetrombopag is a TPO receptor agonist approved in China in 2021 for idiopathic thrombocytopenic purpura (ITP) and second-line severe aplastic anemia (SAA). Indications of chemotherapy-induced thrombocytopenia (CIT), pediatric/juvenile ITP and naive severe aplastic anemia are under development. Hetrombopag was granted Orphan Drug Designation by FDA for the treatment of CIT. Cyclosporine A is a calcineurin inhibitor, which has an effect on reducing T-cell proliferation and activation, can reverse pancytopenia and alleviate transfusion requirements in NSAA.
Primary Outcome Measure Information:
Title
Overall response rate
Description
Percentage of patients with hematological response. Hematological response is evaluated by hemoglobin, platelet and neutrophil count in the routine blood test.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Robust response rate
Description
Percentage of patients with robust response, including complete response, near complete response, very good partial response(VGPR) and Meaningful partial response(mPR). These are evaluated by hemoglobin, platelet and neutrophil count in the routine blood test.
Time Frame
24 weeks
Title
Proportion of patients with abnormal karyotype changes
Description
The abnormal karyotype was examined by karyotype test
Time Frame
Baseline and 24 weeks
Title
Time duration for patients achieving hematological response
Description
Duration time was calculated from response to relapse.
Time Frame
A minimum of 2 years of planned follow-up
Title
Change of the health-related quality of life
Description
Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36) is used to assess the health-related quality of life of patients. The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100. Lower scores = more disability, higher scores = less disability
Time Frame
Baseline and 24 weeks
Title
Incidence of the adverse event
Description
Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event.
Time Frame
24 weeks
Title
Severity of the adverse event
Description
Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the severity.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Willing and able to comply with the requirements for this study and written informed consent. Male or female age ≥ 18 years Diagnosis of untreated non severe aplastic anemia. Platelet counts < 50 x 10^9/L at least 2 times consecutively (time interval ≥ 1 week) Exclusion Criteria: Receive immunosuppressive therapy more than 4 weeks before enrollment Treatment with TPO-RA within 1 week before enrollment Inherited bone marrow failure syndromes Bone marrow fibrosis grade ≥ 2 The presence of hemolytic PNH clone The presence of clonal karyotypic abnormalities (del(20q), +8 and -Y are not included in this category) Previously treated with TPO-RA ≥ 4 weeks Previously received immunosuppressive therapy ≥ 12 weeks Ferritin > 1000 ng/ml (The increased level of Ferritin led by infection is not included in this category) Have an allergy to eltrombopag or any other part of this medicine. History of radiotherapy and chemotherapy for malignant solid tumors Cytopenia caused by other non-hematologic diseases, including liver cirrhosis, active rheumatic connective tissue disease, and persistence of infectious diseases, etc Abnormal liver function: ALT or AST > 3 ULN, or TBil > 1.5 ULN after treatment. Abnormal kidney function: Creatinine clearance < 30 ml/min, or serum creatinine (sCr) >1.5 ULN Patients with diabetic nephropathy, neuropathy, or eye disease Patients with poorly controlled hypertension or cardiac arrhythmia Patients with congestive heart failure and the NYHA grade ≥ 3 historically or currently, and LVEF < 45% within 4 weeks before enrollment History of arteriovenous thrombosis within 1 year before enrollment Participation in another clinical trial within 4 months before the start of this trial Pregnant or breast-feeding patients Patients considered to be ineligible for the study by the investigator for reasons other than the above
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lele Zhang, PhD
Phone
‭15811139278‬
Email
zhanglele@ihcams.ac.cn
Facility Information:
Facility Name
Tangshan Central Hospital
City
Tangshan
State/Province
Hebei
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Li
Phone
15030531816
Email
769164130@qq.com
Facility Name
Zhoukou Central Hospital
City
Zhoukou
State/Province
Henan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qian Liang, PhD
Phone
‭15703815972‬
Email
lqw141230@163.com
Facility Name
The Second Affilated Hospital of Shandong First Medical University
City
Tai'an
State/Province
Shandong
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hong Zhang
Phone
18505386878
Email
tyfyzhh@163.com
Facility Name
Regenerative Medicine Center
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lele Zhang, PhD
Phone
15811139278‬
Email
zhanglele@ihcams.ac.cn

12. IPD Sharing Statement

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Herombopag Added to Cyclosporine in Non Severe Aplastic Anemia

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